The present invention further relates to a process for the preparation of the spirolactones of formula I.
The compounds of formula I are intermediates useful for the preparation of the spirolactone compounds of formula II.

The compounds of formula II, along with their use as NPY5 antagonists for treating bulimia, obesity or diabetes, were disclosed in U.S. Pat. No. 6,335,345, which is incorporated by reference herein in its entirety, and in WO 01/14376 (published on Mar. 2, 2001). The compounds of formula II are also useful as agents for the treatment of various diseases related to NPY, including, but not limited to, cardiovascular disorders, such as hypertension, nephropathy, heart disease, vasospasm, arteriosclerosis and the like, central nervous system disorders, such as bulimia, depression, anxiety, seizure, epilepsy, dementia, pain, alcoholism, drug withdrawal and the like, metabolic diseases such as obesity, diabetes, hormone abnormality, hypercholesterolemia, hyperlipidemia and the like, sexual and reproductive dysfunction, gastrointestinal disorder, respiratory disorder, inflammation or glaucoma, and the like.
U.S. Pat. No. 6,335,345, which is incorporated by reference herein in its entirety, and WO 01/14376, describe a process for preparing the compounds of formula II from the spirolactone of formula I.
U.S. Pat. No. 6,388,077 and U.S. Ser. No. 60/352,451 describe processes for preparing the compounds of formula I. However, a large number of synthetic transformations are required (the longest linear sequence being about 7 steps) with an overall yield between about 15-20%.
With the present invention, there is produced more efficiently the compound of structural formula I in considerably fewer chemical steps utilizing fewer chemical reagents. For method A, the longest linear sequence is 4 steps with an overall yield of about 27%. For method B, the longest linear sequence is 4 steps with an overall yield of about 24%.
Processes for the preparation of organolithium reagents, 3-benzylpicolinic and 3-benzylisonicotinic acids, as well as lactone ring formation, are described in Synthetic Communications, 20 (17), pp. 2623-2629 (1990). Processes for the ortho-lithiation of N-propenylbenzamides and N-propenyl-o-toluamides are described in J. Org. Chem., vol. 57, pp. 2700-2705 (1992).